Toxicity Evaluation of a Novel Magnetic Resonance Imaging Marker, CoCl2-N-Acetylcysteine, in Rats.

C4 (cobalt dichloride-N-acetylcysteine [1% CoCl:2% NAC]) is a novel magnetic resonance imaging contrast marker that facilitates visualization of implanted radioactive seeds in cancer brachytherapy. We evaluated the toxicity of C4. Rats were assigned to control (0% CoCl:NAC), low-dose (0.

Erratum to: Pharmacokinetic evaluation of nanoparticle albumin-bound paclitaxel delivered via hepatic arterial infusion in patients with predominantly hepatic metastases.

In the original article, corresponding author's given name and family name are flipped. It should be "Siqing Fu" rather than "Fu Siqing".

Pharmacokinetic evaluation of nanoparticle albumin-bound paclitaxel delivered via hepatic arterial infusion in patients with predominantly hepatic metastases.

Purpose: Cancer patients with predominantly hepatic metastases have poor outcomes and limited options. Hepatic arterial infusion (HAI) of a therapeutic agent may be an appropriate option for producing increased drug concentrations at the tumor sites while reducing systemic adverse effects in normal tissues.

Methods: Patients with predominantly hepatic metastases (n = 48) were placed in 6 groups according to nanoparticle albumin-bound paclitaxel (nab-paclitaxel) dose level using a 3 + 3 design plus dose expansion for responsive tumor types.

An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma.

Ewing sarcoma is a transcription factor-mediated pediatric bone tumor caused by a chromosomal translocation of the EWSR1 gene and one of several genes in the ETS family of transcription factors, typically FLI1 or ERG. Full activity of the resulting oncogenic fusion protein occurs only after binding RNA helicase A (RHA), and novel biologically targeted small molecules designed to interfere with that interaction have shown early promise in the preclinical setting. Herein, we demonstrate marked preclinical antineoplastic activity of an orally bioavailable formulation of YK-4-279 and identify mechanisms of acquired chemotherapy resistance that may be exploited to induce collateral sensitivity.

A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.

Purpose: Previous studies suggest a potential therapeutic role for mTOR inhibition in lymphoid malignancies. This single-center phase I/II study was designed to test the safety and efficacy of the mTOR inhibitor everolimus in combination with HyperCVAD chemotherapy in relapsed/refractory acute lymphoblastic leukemia (ALL).

Experimental Design: Twenty-four patients were treated; 15 received everolimus 5 mg/day and 9 received 10 mg/day with HyperCVAD.

SU2C phase Ib study of paclitaxel and MK-2206 in advanced solid tumors and metastatic breast cancer.

Background: There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer.

Methods: Patients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalated at 90mg, 135mg, and 200mg.

Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

Background And Purpose: Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery.

Dual inhibition of the vascular endothelial growth factor pathway: a phase 1 trial evaluating bevacizumab and AZD2171 (cediranib) in patients with advanced solid tumors.

Background: The current study was conducted to evaluate the safety and biological activity of dual inhibition of the vascular endothelial growth factor (VEGF) pathway with combined bevacizumab and cediranib (a VEGF receptor tyrosine kinase inhibitor).

Methods: This was a 3 + 3 dose escalation study in patients with advanced solid tumors. Cediranib was given orally daily for 21 days and bevacizumab intravenously every 2 weeks.

Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

Purpose: Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days.

Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma.

Purpose: This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma.

Patients And Methods: Patients with stage IV or unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.

Busulfan and metronidazole: an often forgotten but significant drug interaction.

Objective: To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM).

Case Summary: A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.

Phase I trial of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel: toxicity, pharmacokinetics, and activity.

Because liver involvement in patients with metastatic cancer has limited options and poor outcomes, we conducted a phase I study to determine the safety, activity, and pharmacokinetic characteristics of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel (HAI nab-paclitaxel). Cohorts of three patients having predominant hepatic metastases received HAI nab-paclitaxel at three dose levels (180, 220, and 260 mg/m(2), respectively) infused for more than 1 hour every 3 weeks (3 + 3 design). Some patients participated in comparative pharmacokinetic studies (i.

Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma.

Background: Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting.

Methods: Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG).

Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions.

Epidemiologic and preclinical data support the oral cancer prevention potential of green tea extract (GTE). We randomly assigned patients with high-risk oral premalignant lesions (OPL) to receive GTE at 500, 750, or 1,000 mg/m(2) or placebo thrice daily for 12 weeks, evaluating biomarkers in baseline and 12-week biopsies. The OPL clinical response rate was higher in all GTE arms (n = 28; 50%) versus placebo (n = 11; 18.

T cell CD3 receptor zeta (TCRzeta)-chain expression in children with idiopathic nephrotic syndrome.

Children with idiopathic nephrotic syndrome (INS) have an increased risk of developing life-threatening infections. Several studies have demonstrated functional abnormalities in the T lymphocytes of patients with nephrotic syndrome. Although T cells are activated in INS during relapse, as indicated by an increased expression of interleukin (IL)-2 receptor, these cells have a decreased ability to proliferate.

Decreased expression of CD3zeta and nuclear transcription factor kappa B in patients with pulmonary tuberculosis: potential mechanisms and reversibility with treatment.

Background: The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases.

L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes.

Engagement of the T cell receptor (TCR) by antigen or anti-CD3 antibody results in a cycle of internalization and re-expression of the CD3zeta. Following internalization, CD3zeta is degraded and replaced by newly synthesized CD3zeta on the cell surface. Here, we provide evidence that availability of the amino acid L-arginine modulates the cycle of internalization and re-expression of CD3zeta and cause T cell dysfunction.

L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes.

L-Arginine plays a central role in the normal function of several organs including the immune system. It is metabolized in macrophages by inducible nitric oxide synthase to produce nitric oxide, important in the cytotoxic mechanisms, and by arginase I (ASE I) and arginase II (ASE II) to synthesize L-ornithine and urea, the first being the precursor for the production of polyamines needed for cell proliferation. L-Arginine availability can modulate T cell function.

Regulation of T cell receptor CD3zeta chain expression by L-arginine.

L-Arg plays a central role in the normal function of several organ systems including the immune system. L-Arg can be depleted by arginase I produced by macrophages and hepatocytes in several disease states such as trauma and sepsis and following liver transplantation. The decrease in L-Arg levels induces a profound decrease in T cell function through mechanisms that have remained unclear.